More Than Skin Deep David Woodley continues the pursuit of researching conditions of the skin, coupled with the innovations of gene therapy.
by Alfred Kildow
Children born with a certain genetic error develop a disease in which chronic, incurable blisters wound the skin and leave large scars. Ultimately-usually in their thirties-they die from aggressive cancers that spread from their skin and invade other organs.
Someday, this disease-epidermolysis bullosa (EB)-may be cured by gene therapy. In such a case, physicians would transplant onto the wounds of EB patients grafts of their own skin cells in which the genetic defect is corrected. The hope is that the "gene corrected" skin transplants would halt the endless cycles of blisters and heal the wounds.
If this scenario comes to pass, it may well come from the laboratory of David T. Woodley, M.D., who joined the USC/Norris Comprehensive Cancer Center this January. He brought with him two Ph.D. colleagues from Chicago-Mei Chen and Wei Li-and two research studies funded by the National Institutes of Health.
Woodley is quick to acknowledge that one of his reasons for wanting to come to Norris is the world-class gene therapy effort already underway at USC, an effort that includes faculty throughout the School of Medicine, including researchers W. French Anderson, M.D., Nori Kasahara, M.D., Ph.D., Donald Kohn, M.D., and Robertson Parkman, M.D., the latter two on the staff at Childrens Hospital Los Angeles.
Woodley is a professor in the Department of Medicine and co-chief (with Arnold Gurevitch, M.D.) of the division of dermatology. His colleagues Wei Li and Mei Chen will become associate professors in the division, as well as members of the Cancer Center research staff.
"We will soon have a dermatology division that functions in the classic mold of USC/Norris translational medicine," Woodley says. "We will have a strong research capability that we will couple with USC's gene therapy programs. We will take this research as quickly as we can from laboratory bench to the patients' bedsides."
He explains that resident physicians are already working in the department, and he plans to have graduate students in the department by summer.
Woodley is widely known for his expertise in understanding blistering disorders of skin, wound healing and skin cancer. He is also expert in the use of phototherapy, using artificial ultraviolet light to treat conditions of the skin.
Woodley and his colleagues have cultured human keratinocytes, a type of skin cell, and used these cultured cells to heal chronic skin wounds and the wounds of burn victims. His team was among the first to use this type of therapy.
One of his current NIH-sponsored research programs is to study how skin cells migrate to resurface skin wounds. In this work, the Woodley laboratory examines how normal skin epithelial cells migrate along the connective tissue of wound beds to resurface skin wounds. Similarly, skin cancer cells migrate along these same inner connective tissues and coalesce to form cancers elsewhere on the body.
His second research program involves a type of collagen, called type VII, that helps to anchor the outer layer of the skin, the epidermis, onto the inner connective tissue layer, the dermis. His laboratory, in collaboration with the laboratory of Jouni Uitto, M.D., at Thomas Jefferson Medical College, has cloned the human gene that makes type VII collagen. It is this gene that contains the mutations that result in EB disease.
Woodley and Chen have made a "mini gene" that causes type VII collagen to be produced in skin cells. In his laboratory at Northwestern, the scientists have introduced these mini genes into patches of skin in laboratory dishes. These transfected skin patches have expressed the new gene continuously.
This leads Woodley to believe that he can use patches of skin from EB patients as carriers to transplant the mini gene onto EB patients. Because the patches would be the patients' own skin, these cultured skin transplants would not be rejected by the patient's immune system.
This is the work that Woodley, Li and Chen will do at USC/Norris.
The two projects - skin cell migration and type VII collagen gene therapy-dovetail together, Woodley explains. Children with EB suffer from chronic wounds that form aggressive skin cancers that metastasize.
"Therefore, the work on cell migration through connective tissues has relevance to skin cancer and wound healing because these are the two essential features of EB," Woodley says.
Woodley has been chair of the Department of Dermatology at Northwestern since 1992. Prior to that he was a professor and associate chair of the Department of Dermatology at Stanford University. He received his undergraduate education at Washington University, St. Louis, and his M.D. at the University of Missouri. He has held faculty positions, research fellowships and residencies at many institutions, among them the University of North Carolina, NIH, the University of Paris (France) and Mt. Sinai and New York Hospitals in New York.
Chen and Li are from the People's Republic of China, where both received their undergraduate educations. Li, who has a faculty position as an associate professor in the USC Department of Medicine, received a master's degree in developmental biology and cancer from Xinjiang University, before completing his Ph.D. in 1991 at the Albert Einstein College of Medicine in New York. He taught at the New York University Medical Center from 1990 until 1993, before moving to the University of Chicago in 1993, where he has been an assistant professor in the Ben May Institute for Cancer Research.
Chen received her bachelor's degree in biology in 1984 and a master's in cell biology in 1987 from the University of Science and Technology of China. She received her Ph.D. in cell and molecular biology in 1990 from the Albert Einstein College of Medicine in New York. She held post-doctoral and research appointments at Sloan-Kettering Cancer Center and Cornell University Medical College in New York, before joining the research staff at the University of Chicago in 1993. She moved to Woodley's Dermatology Department at Northwestern in 1994. She is an associate professor in the USC Department of Medicine.